Disruption of a self-amplifying catecholamine loop reduces cytokine release syndrome.

Cytokine release syndrome (CRS) is a life-threatening complication of several new immunotherapies used to treat cancers and autoimmune diseases1-5. Here we report that atrial natriuretic peptide can protect mice from CRS induced by such agents by reducing the levels of circulating catecholamines. Catecholamines were found to orchestrate an immunodysregulation resulting from oncolytic bacteria and lipopolysaccharide through a self-amplifying loop in macrophages. Myeloid-specific deletion of tyrosine hydroxylase inhibited this circuit. Cytokine release induced by T-cell-activating therapeutic agents was also accompanied by a catecholamine surge and inhibition of catecholamine synthesis reduced cytokine release in vitro and in mice. Pharmacologic catecholamine blockade with metyrosine protected mice from lethal complications of CRS resulting from infections and various biotherapeutic agents including oncolytic bacteria, T-cell-targeting antibodies and CAR-T cells. Our study identifies catecholamines as an essential component of the cytokine release that can be modulated by specific blockers without impairing the therapeutic response.

Exploring transcriptional regulators Ref-1 and STAT3 as therapeutic targets in malignant peripheral nerve sheath tumours.

BACKGROUND: MPNST is a rare soft-tissue sarcoma that can arise from patients with NF1. Existing chemotherapeutic and targeted agents have been unsuccessful in MPNST treatment, and recent findings implicate STAT3 and HIF1-α in driving MPNST. The DNA-binding and transcriptional activity of both STAT3 and HIF1-α is regulated by Redox factor-1 (Ref-1) redox function. A first-generation Ref-1 inhibitor, APX3330, is being tested in cancer clinical trials and could be applied to MPNST. METHODS: We characterised Ref-1 and p-STAT3 expression in various MPNST models. Tumour growth, as well as biomarkers of apoptosis and signalling pathways, were measured by qPCR and western blot following treatment with inhibitors of Ref-1 or STAT3. RESULTS: MPNSTs from Nf1-Arfflox/floxPostnCre mice exhibit significantly increased positivity of p-STAT3 and Ref-1 expression when malignant transformation occurs. Inhibition of Ref-1 or STAT3 impairs MPNST growth in vitro and in vivo and induces apoptosis. Genes highly expressed in MPNST patients are downregulated following inhibition of Ref-1 or STAT3. Several biomarkers downstream of Ref-1 or STAT3 were also downregulated following Ref-1 or STAT3 inhibition. CONCLUSIONS: Our findings implicate a unique therapeutic approach to target important MPNST signalling nodes in sarcomas using new first-in-class small molecules for potential translation to the clinic.

Feasibility of using NF1-GRD and AAV for gene replacement therapy in NF1-associated tumors.

Neurofibromatosis type 1, including the highly aggressive malignant peripheral nerve sheath tumors (MPNSTs), is featured by the loss of functional neurofibromin 1 (NF1) protein resulting from genetic alterations. A major function of NF1 is suppressing Ras activities, which is conveyed by an intrinsic GTPase-activating protein-related domain (GRD). In this study, we explored the feasibility of restoring Ras GTPase via exogenous expression of various GRD constructs, via gene delivery using a panel of adeno-associated virus (AAV) vectors in MPNST and human Schwann cells (HSCs). We demonstrated that several AAV serotypes achieved favorable transduction efficacies in those cells and a membrane-targeting GRD fused with an H-Ras C-terminal motif (C10) dramatically inhibited the Ras pathway and MPNST cells in a NF1-specific manner. Our results opened up a venue of gene replacement therapy in NF1-related tumors.

Impacts of Projected Climate Warming and Wetting on Soil Microbial Communities in Alpine Grassland Ecosystems of the Tibetan Plateau.

Climate change is projected to have impacts on precipitation and temperature regimes in drylands of high elevation regions, with especially large effects in the Qinghai-Tibetan Plateau. However, there was limited information about how the projected climate change will impact on the soil microbial community and their activity in the region. Here, we present results from a study conducted across 72 soil samples from 24 different sites along a temperature and precipitation gradient (substituted by aridity index ranging from 0.079 to 0.89) of the Plateau, to assess how changes in aridity affect the abundance, community composition, and diversity of bacteria, ammonia-oxidizers, and denitrifers (nirK/S and nosZ genes-containing communities) as well as nitrogen (N) turnover enzyme activities. We found V-shaped or inverted V-shaped relationships between the aridity index (AI) and soil microbial parameters (gene abundance, community structures, microbial diversity, and N turnover enzyme activities) with a threshold at AI = 0.27. The increasing or decreasing rates of the microbial parameters were higher in areas with AI < 0.27 (alpine steppes) than in mesic areas with 0.27 < AI < 0.89 (alpine meadow and swamp meadow). The results indicated that the projected warming and wetting have a strong impact on soil microbial communities in the alpine steppes.

Contribution of Anammox to Nitrogen Removal in Two Temperate Forest Soils.

UNLABELLED: Anaerobic ammonium oxidation with nitrite reduction to dinitrogen (termed anammox) has been reported to be an important process for removing fixed nitrogen (N) in marine ecosystems and in some agricultural and wetland soils. However, its importance in upland forest soils has never been quantified. In this study, we evaluated the occurrence of anammox activity in two temperate forest soils collected from northeastern China. With (15)N-labeled NO3 (-) incubation, we found that the combined potential of the N2 production rates of anammox and codenitrification ranged from 0.01 ± 0.01 to 1.2 ± 0.18 nmol N per gram of soil per hour, contributing 0.5% to 14.4% of the total N2 production along the soil profile. Denitrification was the main pathway of N2 production and accounted for 85.6% to 99.5% of the total N2 production. Further labeling experiments with (15)NH4 (+) and (15)NO2 (-) indicated that codenitrification was present in the mixed forest soil. Codenitrification and anammox accounted for 2% to 12% and 1% to 7% of the total N2 production, respectively. Two anammox species, "Candidatus Brocadia fulgida" and "Candidatus Jettenia asiatica," were detected in this study but in very low abundance (as indicated by the hzsB gene). Our results demonstrated that the anammox process occurs in forest soils, but the contribution to N2 loss might be low in these ecosystems. More research is necessary to determine the activities of different N2 releasing pathways in different forest soils. IMPORTANCE: In this study, we examined the anammox activity in temperate upland forest soils using the (15)N isotope technique. We found that the anammox process contributed little to the N2 production rate in the studied forest soil. Two anammox organisms, "Candidatus Brocadia fulgida" and "Candidatus Jettenia asiatica," were detected. In addition, we found that codenitrification was another N2 production pathway in forest soils. Our results could contribute to the understanding of soil gaseous N losses and microbial controls in forest soils.

The operating performance of a biotrickling filter with Lysinibacillus fusiformis for the removal of high-loading gaseous chlorobenzene.

Removal of gaseous chlorobenzene (CB) by a biotrickling filter (BTF) filled with modified ceramics and multi-surface hollow balls during gas-liquid mass transfer at the steady state was by microbial degradation rather than dissolution in the spray liquid or emission into the atmosphere. The BTF was flexible and resistant to the acid environment of the spray liquid, with the caveat that the spray liquid should be replaced once every 6-7 days. The BTF, loaded with Lysinibacillus fusiformis, performed well for purification of high-loading CB gas. The maximum CB gas inlet loading rate, 103 g m(-3) h(-1), CB elimination capacity, 97 g m(-3) h(-1), and CB removal efficiency, 97.7 %, were reached at a spray liquid flow rate of 27.6 ml min(-1), an initial CB concentration of up to 1,300 mg m(-3), and an empty bed retention time of more than 45 s.

Elemene Antitumor Drugs Development Based on "Molecular Compatibility Theory" and Clinical Application: A Retrospective and Prospective Outlook.

Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian, introduced the innovative concept of "molecular compatibility theory" by combining Chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of Chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory".

[Differentiation of axillary inflammatory and metastatic lymph nodes with diffusion-weighted imaging in animal modes].

OBJECTIVE: To evaluate the value of diffusion-weighted imaging (DWI) in the differentiation of axillary inflammatory hyperplastic and metastatic lymph nodes. METHODS: Forty female New Zealand white rabbits were divided randomly into 2 groups (n = 20 each). And the animal models of axillary inflammatory hyperplastic and metastatic lymph nodes were established. All successfully implanted models received conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) examinations. The features of signal intensity and shapes of lymph nodes were observed in two groups. The sizes of lymph nodes were measured on the selected axial T(2)WI. The signal intensity and appearance diffusion coefficient (ADC) value of lymph nodes and dorsal muscle at the same slice were measured on the selected T(2)WI, DWI and ADC map respectively. The relative signal intensity (rSIT(2)WI, rSIDWI) and relative ADC (rADC) value of lymph nodes to dorsal muscle were calculated and compared. The diagnostic efficacy of differentiating benign and malignant lymph nodes was analyzed with rADC value through the receiver operating characteristic curve. The correlation between rADC value and cell density was assessed with pathological findings as reference standard. RESULTS: The differences of size, rSIT(2)WI and rSIDWI were not statistically significant between two groups. The rADC value of inflammatory lymph nodes was greater than that of metastatic lymph nodes (0.91 ± 0.14 vs 0.64 ± 0.18). Significant difference existed (t = 3.879, P = 0.03). But there was a little overlap between two groups. With 0.78 as the diagnostic threshold of rADC value, the sensibility and specificity was 86.2% and 74.4% respectively. The correlation between rADC value and cell density of inflammatory hyperplastic and metastatic lymph nodes was significantly inverse (r = -0.53, P = 0.003). CONCLUSIONS: As compared with the routine MRI sequence, rADC value has a higher diagnostic efficacy in the differentiation of benign and malignant lymph nodes. Cell density may be the most important influencing factor for the differences of rADC value between two groups of lymph nodes.

Neutrophil depletion enhanced the Clostridium novyi-NT therapy in mouse and rabbit tumor models.

BACKGROUND: Hypoxia is a prominent feature of solid tumors and can function as fertile environment for oncolytic anaerobic bacteria such as Clostridium novyi-NT (C. novyi-NT) where it can induce tumor destruction in mice and patients. However, two major obstacles have limited its use, namely the host inflammatory response and the incomplete clearance of normoxic tumor areas. METHODS: In this study, we first used a subcutaneous tumor model of a glioblastoma (GBM) cell line in immunocompetent mice to investigate the local distribution of tumor hypoxia, kinetics of C. novyi-NT germination and spread, and the local host immune response. We subsequently applied the acquired knowledge to develop a C. novyi-NT therapy in an orthotopic rabbit brain tumor model. RESULTS: We found that local accumulation of granular leukocytes, mainly neutrophils, could impede the spread of bacteria through the tumor and prevent complete oncolysis. Depletion of neutrophils via anti-Ly6G antibody or bone marrow suppression using hydroxyurea significantly improved tumor clearance. We then applied this approach to rabbits implanted with an aggressive intracranial brain tumor and achieved long-term survival in majority of the animals without apparent toxicity. CONCLUSION: These results indicated that depleting neutrophils can greatly enhance the safety and efficacy of C. novyi-NT cancer therapy for brain tumors.

2,2'-((1R,3R,4S)-4-methyl-4-vinylcyclohexane-1,3-diyl) bis(prop-2-en-1-amine), a bisamino derivative of ß-Elemene, inhibits glioblastoma growth through downregulation of YAP signaling.

ß-Elemene, a compound extracted from Chinese herb Curcuma wenyujin, has been demonstrated with antitumor effects in various cancers, including glioblastoma (GBM), a primary brain tumor with high morbidity and mortality. In this study, we reported a bisamino derivative of ß-Elemene, 2, 2'-((1R, 3R, 4S)-4-methyl-4-vinylcyclohexane-1, 3-diyl) bis(prop-2-en-1-amine) (compound 1), displayed a better anti-GBM effect than ß-Elemene with lower concentration. GBM cell lines (C6 and U87) were treated with compound 1 and subsequently analyzed by several assays. Compound 1 significantly inhibited the migration of C6 and U87 cells based on wound healing assay, transwell assay and inverted migration assay. Furthermore, colony formation assay, immunostaining and flow cytometry assays revealed that compound 1 significantly inhibited the proliferation of GBM cells. In addition, compound 1 induced the apoptosis of GBM cells. Mechanistically, we found Yes-associated protein (YAP) was down-regulated in compound 1-treated GBM cells, and the overexpression of YAP partially rescued the anti-GBM effects of compound 1. Finally, compound 1 suppresses the GBM growth in xenograft model through inactivation YAP signaling. Taken together, these results reveal that a novel derivative of ß-Elemene, compound 1, exhibits more potent anti-GBM activity than ß-Elemene through inactivating YAP signaling pathway, which will provide novel strategies for the treatment of GBM.

Mitochondrial dysfunction in human breast cancer cells and their transmitochondrial cybrids.

Somatic mitochondrial DNA alterations have been found in all types of cancer. To better understand the role of mitochondria and their involvement in the pathogenic mechanisms of cancer development, the effects of cancer mitochondria were investigated in a defined nuclear background using a transmitochondrial cybrid system. Our results demonstrated that cancer mitochondria confer a significant reduction in cell growth when cells are metabolically stressed in a galactose medium. Activities of the respiratory chain complexes, cellular oxygen consumption, and ATP synthesis rates were found to be much lower in breast cancer cells, than those in normal breast epithelial cells of MCF-10A (10A). These results suggest that there is reduced mitochondrial function in the studied breast cancer cell lines. Similarly reduced mitochondrial function was observed in cybrids containing cancer mitochondria. Novel tRNA mutations were also identified in two breast cancer cell lines, possibly responsible for the observed mitochondrial dysfunction. We conclude that altered mitochondria in cancer cells may play a crucial role in tumor development.

SMIF, a Smad4-interacting protein that functions as a co-activator in TGFbeta signalling.

Proteins of the transforming growth factor beta(TGFbeta) superfamily regulate diverse cellular responses, including cell growth and differentiation. After TGFbeta stimulation, receptor-associated Smads are phosphorylated and form a complex with the common mediator Smad4. Here, we report the cloning of SMIF, a ubiquitously expressed, Smad4-interacting transcriptional co-activator. SMIF forms a TGFbeta/bone morphogenetic protein 4 (BMP4)-inducible complex with Smad4, but not with others Smads, and translocates to the nucleus in a TGFbeta/BMP4-inducible and Smad4-dependent manner. SMIF possesses strong intrinsic TGFbeta-inducible transcriptional activity, which is dependent on Smad4 in mammalian cells and requires p300/CBP. A point mutation in Smad4 abolished binding to SMIF and impaired its activity in transcriptional assays. Overexpression of wild-type SMIF enhanced expression of TGFbeta/BMP regulated genes, whereas a dominant-negative SMIF mutant suppressed expression. Furthermore, dominant-negative SMIF is able to block TGFbeta-induced growth inhibition. In a knockdown approach with morpholino-antisense oligonucleotides targeting zebrafish SMIF, severe but distinct phenotypic defects were observed in zebrafish embryos. Thus, we propose that SMIF is a crucial activator of TGFbeta signalling.

A therapeutic strategy for choroidal neovascularization based on recruitment of mesenchymal stem cells to the sites of lesions.

Choroidal neovascularization (CNV) is a common cause of severe and irreversible visual loss; however, the treatment of CNV has been hindered by its complex and poorly understood pathogenesis. It has been postulated that bone marrow (BM)-derived cells (BMCs) contribute to CNV, but little is known about the role of mesenchymal stem cells (MSCs) in CNV and their therapeutic potential for CNV treatment. We found that BM-derived MSCs transplanted by intravenous injection into laser-induced CNV mouse models were specifically recruited into CNV lesions, where they differentiated into multiple cell types and participated in the development of neovascularization, without stagnation in other organs. By taking advantage of this recruitment potential, engineered MSCs were used to produce the antiangiogenic pigment epithelial-derived factor (PEDF) at the CNV sites, thereby inhibiting the growth of CNVs and stimulating regressive features. Further studies indicated that the effect may be mediated, at least partly, by retinal pigment epithelial (RPE) cells, which function as important regulators for CNV development. These results suggest that MSCs contribute to CNV and could serve as delivery vehicles of antiangiogenic agents for the treatment of a range of CNV-associated diseases.

Agronomic and economical characterizations of a two-harvest regime for oat forage in cold regions of Northern China.

The natural grasslands in northern China have been seriously degraded due mainly to overgrazing and climate change in recent decades, leading to shortage of forage supply to animal husbandry. To maximize forage production, we developed a two-harvest regime of oat forage by sowing in spring in an alpine region of Hulun Buir, northern China, using two oat early maturation species. The agronomic characteristics and forage quality of the two-harvest regime were evaluated across three constructive years from 2017 to 2019. Compared to the traditional one-harvest regime, the production, resource use efficiency, and economic benefits were compared and quantified for both oat species across the 3 years. Dry weight forage by the two-harvest regime was increased by 17.5-18.5%, while crude protein was increased by 25.1-30.0%. Growing days by the two-harvest regime was increased by 36.7% on average, nitrogen fertilizer use efficiency was enhanced by 25.1-30.0%, while water use efficiency was not significantly changed. The two-harvest regime also increased the net profit by 28.0%. Taken together, our results reveal that the two-harvest regime of forage production in the cold region of northern China is a promising practice with high forage yield, nutritional value, and nitrogen fertilizer use efficiency as well as economic profit.

LLL12B, a small molecule STAT3 inhibitor, induces growth arrest, apoptosis, and enhances cisplatin-mediated cytotoxicity in medulloblastoma cells.

Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor and an oncogene product, which plays a pivotal role in tumor progression. Therefore, targeting persistent STAT3 signaling directly is an attractive anticancer strategy. The aim of this study is to test the efficacy of a novel STAT3 small molecule inhibitor, LLL12B, in suppressing medulloblastoma cells in vitro and tumor growth in vivo. LLL12B selectively inhibited the induction of STAT3 phosphorylation by interleukin-6 but not induction of STAT1 phosphorylation by INF-γ. LLL12B also induced apoptosis in human medulloblastoma cells. In addition, LLL12B exhibited good oral bioavailability in vivo and potent suppressive activity in tumor growth of medulloblastoma cells in vivo. Besides, combining LLL12B with cisplatin showed greater inhibition of cell viability and tumorsphere formation as well as induction of apoptosis comparing to single agent treatment in medulloblastoma cells. Furthermore, LLL12B and cisplatin combination exhibited greater suppression of medulloblastoma tumor growth than monotherapy in vivo. The present study supported that LLL12B is a novel therapeutic agent for medulloblastoma and the combination of LLL12B with a chemotherapeutic agent cisplatin may be an effective approach for medulloblastoma therapy.

Mebendazole and temozolomide in patients with newly diagnosed high-grade gliomas: results of a phase 1 clinical trial.

BACKGROUND: Mebendazole is an anthelmintic drug introduced for human use in 1971 that extends survival in preclinical models of glioblastoma and other brain cancers. METHODS: A single-center dose-escalation and safety study of mebendazole in 24 patients with newly diagnosed high-grade gliomas in combination with temozolomide was conducted. Patients received mebendazole in combination with adjuvant temozolomide after completing concurrent radiation plus temozolomide. Dose-escalation levels were 25, 50, 100, and 200 mg/kg/day of oral mebendazole. A total of 15 patients were enrolled at the highest dose studied of 200 mg/kg/day. Trough plasma levels of mebendazole were measured at 4, 8, and 16 weeks. RESULTS: Twenty-four patients (18 glioblastoma and 6 anaplastic glioma) were enrolled with a median age of 49.8 years. Four patients (at 200 mg/kg) developed elevated grade 3 alanine aminotransferase (ALT) and/or aspartate transaminase (AST) after 1 month, which reversed with lower dosing or discontinuation. Plasma levels of mebendazole were variable but generally increased with dose. Kaplan-Meier analysis showed a 21-month median overall survival with 41.7% of patients alive at 2 years and 25% at 3 and 4 years. Median progression-free survival (PFS) from the date of diagnosis for 17 patients taking more than 1 month of mebendazole was 13.1 months (95% confidence interval [CI]: 8.8-14.6 months) but for 7 patients who received less than 1 month of mebendazole PFS was 9.2 months (95% CI: 5.8-13.0 months). CONCLUSION: Mebendazole at doses up to 200 mg/kg demonstrated long-term safety and acceptable toxicity. Further studies are needed to determine mebendazole's efficacy in patients with malignant glioma.

[Value of diffusion weighted imaging in diagnosis of nodular lesions of thyroid: a preliminary study].

OBJECTIVE: To investigate the value of magnetic resonance diffusion weighted imaging (DWI) in the differential diagnoses of malignant and benign thyroid lesions. METHODS: Using echo planner imaging sequence with b value of 0, 100, 200, 300 and 400 s/mm(2) respectively, DWI was performed in 60 patients of focal thyroid lesions. The diagnosis was confirmed by pathological examination (benign, n = 30; malignant, n = 30). Apparent diffusion coefficient (ADC) values were measured. The differences were analyzed between two groups. RESULTS: With b value of 0, 100, 200, 300 and 400 s/mm(2) respectively, there were statistical differences in ADC values between benign and malignant lesions. The ADC value of malignant lesions was smaller than that of benign lesions (P < 0.05). Among different b values, 400 s/mm(2) was the most optimal one to diagnose thyroid nodular lesions. DWI with a b value of 400 s/mm(2) had a proper signal-to-noise ratio (SNO). And ADC value could be measured correctly. With a b value of 400 s/mm(2) and ADC of 1.475 × 10(-3) mm(2)/s, receiver operating characteristic curve was plotted. In the diagnosis of malignant lesions, the sensitivity and specificity were 93.3% and 96.7% respectively. CONCLUSIONS: The ADC value of malignant thyroid nodular lesions is smaller than that of benign lesions. The values of DWI and ADC are important in the differential diagnoses of nodular thyroid lesions.

Preventative Effect of Mebendazole against Malignancies in Neurofibromatosis 1.

Patients with RASopathy Neurofibromatosis 1 (NF1) are at a markedly increased risk of the development of benign and malignant tumors. Malignant tumors are often recalcitrant to treatments and associated with poor survival; however, no chemopreventative strategies currently exist. We thus evaluated the effect of mebendazole, alone or in combination with cyclooxygenase-2 (COX-2) inhibitors, on the prevention of NF1-related malignancies in a cisNf1+/-;Tp53+/- (NPcis) mouse model of NF1. Our in vitro findings showed that mebendazole (MBZ) inhibits the growth of NF1-related malignant peripheral nerve sheath tumors (MPNSTs) through a reduction in activated guanosine triphosphate (GTP)-bound Ras. The daily MBZ treatment of NPcis mice dosed at 195 mg/kg daily, initiated 60 days after birth, substantially delayed the formation of solid malignancies and increased median survival (p < 0.0001). Compared to placebo-treated mice, phosphorylated extracellular signal-regulated kinase (pERK) levels were decreased in the malignancies of MBZ-treated mice. The combination of MBZ with COX-2 inhibitor celecoxib (CXB) further enhanced the chemopreventative effect in female mice beyond each drug alone. These findings demonstrate the feasibility of a prevention strategy for malignancy development in high-risk NF1 individuals.

Label-Free Detecting of the Compaction and Decompaction of ctDNA Molecules Induced by Surfactants with SERS Based on a nanoPAA-ZnCl2-AuLs Solid Substrate.

DNA molecular compaction/decompaction is of great significance for the exploration of basic life processes, the research of biomedical and genetic engineering, and so forth. However, the detailed mechanism of DNA compaction/decompaction caused by surfactants remains an open and challenging problem that has not been fully solved so far. In this paper, a sort of novel solid substrate, nanoPAA-ZnCl2-AuLs, with good stability and high sensitivity, was prepared by a self-assembly method. Based on this substrate, the surface-enhanced Raman scattering (SERS) technology was employed to investigate characteristics of interactions between DNA molecules and surfactants at a single molecular level. SERS spectra of calf thymus DNA (ctDNA), cetyl trimethyl ammonium bromide (CTAB), and sodium dodecyl sulfate (SDS) with a concentration as low as 10-9 M, and SERS spectra of ctDNA-CTAB and ctDNA-CTAB-SDS composites were collected, respectively. The interactions between ctDNA and surfactants were analyzed by changes in SERS spectra, for example, disappearances and appearances of SERS bands and relative changes of peak intensity, in which CTAB resulted in the compaction of the DNA molecule while SDS induced the decompaction of the ctDNA-CTAB complex. Moreover, UV-visible spectrophotometry was employed to demonstrate the compaction/decompaction of ctDNA molecules caused by surfactants. The local binding modes of ctDNA molecules and surfactant molecules were expounded. This work will be helpful for understanding biological processes such as DNA compaction and recombination within nucleus or/and cells and for the development of gene therapy technologies.